Recently, a new disease concept called Chronic Kidney Disease (CKD) has been identified and has attracted worldwide attention. Chronic Kidney Disease is treated by the use of angiotensin II inhibitors, by diet control by means of rice with low protein content, and by the control of various risk factors. However, 40,000 people undergo dialysis annually, which carries a risk of death as a consequence of cardiovascular disturbance complications, and accordingly there is a demand for a new treatment method. As a treatment method for chronic kidney disease, a method of removing non-transferrin-bound iron (NTBI), and a carbonyl compound that are the main causes of chronic kidney disease is effective.
As a treatment methods of removing iron from a living body (in particular, non-transferrin-bound iron (NTBI)), there are (1) phlebotomy, (2) an iron-limiting diet, (3) medical therapy using an iron chelating agent, and (4) extracorporeal circulating and cleaning therapy. Phlebotomy is good in terms of patient Quality of Life (QOL), but results in side effects such as anemia or hypoproteinemia and can only be applied to patients who do not suffer from anemia. The iron-limiting diet results in side effects such as nutrition imbalance and can only be applied to some hepatic diseases. The medical therapy using an iron chelating agent has a pronounced iron chelating effect and is mainly used with patients who have an iron overload disorder after a blood transfusion. However, it is said that in iron-related organ disorders resulting from a mild iron overload disorder or an iron metabolism disorder, side effects caused by over-chelating occur with high frequency. Further, extracorporeal circulating and cleaning therapy is a method of removing iron (iron ions) by extracorporeal circulation of blood and has a property of enabling the treatment of unstable iron having toxicity in a living body without causing organ toxicity by over-chelating.
As a result, a method of removing non-transferrin-bound iron by extracorporeal circulation and cleaning therapy has been studied. There is a demand for the development of a ligand (iron chelating agent) which specifically and effectively adsorbs non-transferrin-bound iron. In particular, there is a demand for the development of an iron chelating agent capable of trapping only non-transferrin-bound iron without having chelating ability with respect to transferrin-bound iron which is useful for a living body (that is, without trapping transferrin-bound iron).
Further, when chronic kidney disease enters stage 4, load is applied on the remaining nephrons due to the increased number of failed nephrons and thus more nephrons fail; dialysis must be introduced as a result of falling into this vicious circle. On the other hand, in stage 3, the risk of cardiovascular pathology is markedly increased. The dialysis treatment needs be carried out three times per week, and the time required to perform the dialysis is 4 hours and thus the QOL of a patient is decreased, as well as causing the loss of the chance to work. Therefore, as long as treatment is carried out in stage 3, introduction of dialysis and cardiovascular disturbance complications can be prevented, which can lead to a reduction in high medical expenses (it is said that dialysis expenses may exceed 1.2 trillion yen in Japan).
Meanwhile, various proposals have been made in regard to an iron chelating agent capable of chelating iron ions (for example, see Patent Literature 1 to 8).
Further, there is a problem in that, in a method of determining the amount of non-transferrin-bound iron using high-performance liquid chromatography, NTBI values in the blood of healthy persons are often represented as negative values and this leads to a lack of reliability. It is thought that, by clarifying and ameliorating the problems of the NTBI measuring system using HPLC, a stable and highly sensitive NTBI measuring system could be constructed and that, as a result, NTBI values in the blood of healthy persons could be precisely determined.